Hydrochloric Acid → HCID 131724539, compound

HRID 1836581Notes

Reaction equation

HRID 1836581 reaction equation
[ClH:1].Cl.[CH:3]1[CH:12]=[CH:11][C:10]2[CH2:13][CH2:14][CH2:15][N:8]3[C:9]=2[C:4]=1[C@H:5]1[CH2:18][NH:17][CH2:16][C@H:6]1[CH2:7]3.[CH2:19](Br)[CH2:20][CH2:21][CH3:22].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl.CCOCC>O1CCOCC1.C(OCC)(=O)C>[ClH:1].[ClH:1].[CH2:19]([N:17]1[CH2:18][C@H:5]2[C@H:6]([CH2:7][N:8]3[CH2:15][CH2:14][CH2:13][C:10]4[CH:11]=[CH:12][CH:3]=[C:4]2[C:9]3=4)[CH2:16]1)[CH2:20][CH2:21][CH3:22]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 4875Potassium IodideHCID 8002Butyl bromideHCID 11430Potassium CarbonateHCID 131724533HCID 131724533, compound

Product 1

HCID 131724539HCID 131724539, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (±)-cis-5,6,8,8a,9,10,11,11a-octahydro-4H-pyrido[3,2,1-ij]pyrrolo[3,4-c]quinoline free base from EXAMPLE 11 (124 mg, 0.58 mmol) in 5 mL of 1,4-dioxane was added n-butylbromide (79 mg, 0.58 mmol), potassium carbonate (160 mg, 1.16 mmol) and potassium iodide (10 mg, 0.06 mmol) The mixture was stirred at 90° C. for 24 h. The reaction was then cooled, diluted with ethyl acetate, washed with brine, dried (Na2SO4) and concentrated. The residue was purified by preparative HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and the product containing fractions were concentrated, basified with sat'd aq Na2CO3 and extracted twice with ethyl acetate. The organics were washed with brine, dried (Na2SO4) and concentrated to a free base. The residue was taken up in about 4:1 ether/ethanol and then there was added 2M HCl in ether (1.0 mL, 2.0 mmol). The resulting solid was filtered, washed twice with ether and dried in vacuo to afford the title compound of EXAMPLE 104 as an off-white powder. 1H NMR (dmso-D6) δ: 6.90-6.78 (m, 2H), 6.62-6.55 (m, 1H), 4.00-3.93 (m, 1H), 3.85-3.77 (m, 1H), 3.65-3.59 (m, 1H), 3.50-3.35 (m, 2H), 3.15-2.95 (m, 4H), 2.92-2.75 (m, 3H), 2.73-2.63 (m, 2H), 1.95-1.85 (m, 2H), 1.65-1.55 (m, 2H), 1.33-1.22 (m, 2H), 0.91-0.83 (m, 3H). LRMS. (ES)+: 271.2 (M+H)+.

Workup

  1. temperatureThe reaction was then cooled
  2. washwashed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by preparative HPLC (
  6. washC18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and the product
  7. additioncontaining fractions
  8. concentrationwere concentrated
  9. extractionextracted twice with ethyl acetate
  10. washThe organics were washed with brine
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated to a free base
  13. filtrationThe resulting solid was filtered
  14. washwashed twice with ether
  15. customdried in vacuo

Sources & evidence

ORD record
ord-0c82103f81ce4688accadd004a1d3a0d
Source dataset
uspto-grants-2004_08
Patent number
US06777406B2

Reaction notes

Loading…